Expression profiling of human mesoangioblasts indicates that S1P induces differentiation towards smooth muscle cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17596 | GEO | 2011/05/01
SECONDARY ACCESSION(S): PRJNA118505
REPOSITORIES: GEO
Similar Datasets
Project description:cDNA microarray study of human mesoangioblasts treated with 1 µM sphingosine 1-phosphate (S1P) at 6 and 24 h. Agilent whole human genome oligonucleotide microarrays (44 K) were used to examine alterations in gene expression of cells after S1P treatment
2011-05-01 | E-GEOD-17596 | biostudies-arrayexpress
Project description:The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base phosphates, other sphingolipids (including sphingosine, ceramide, and sphingomyelin) were substantially elevated in the serum and /or liver of these mice. This latter increase is consistent with a reutilization of the sphingosine backbone for sphingolipid synthesis due to its inability to exit the sphingolipid metabolic pathway. Furthermore, the S1P lyase deficiency resulted in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Even though lipids in serum and lipid storage were elevated in liver, adiposity was reduced in the S1P lyase-deficient mice. Microarray analysis of lipid metabolism genes in liver showed that the S1P lyase deficiency caused widespread changes in their expression pattern. These results demonstrate that S1P lyase is a key regulator of the levels of multiple sphingolipid substrates and reveal functional links between the sphingolipid metabolic pathway and other lipid metabolic pathways that may be mediated by shared lipid substrates and changes in gene expression programs. The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases. Experiment Overall Design: RNA samples from liver for three sphingosine-1-phosphate lyase knock-out and three WT mice.
2010-02-05 | E-GEOD-18745 | biostudies-arrayexpress
Project description:Background: Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. Objective: To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. Methods: ASM cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and western blotting. Receptor signalling and function was determined by mRNA knockdown and intracellular calcium mobilisation experiments. Results: S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P2 and S1P3 receptors activated intracellular calcium mobilisation and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals. Conclusion: S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma. Airway smooth muscle cells from 3 healthy donors were cultured and stimulated for 4 h with sphingosine-1-phosphate (100 nM) or medium control. Total RNA was extracted and analysed using Affymetrix Human Exon 1.0 ST arrays.
2015-06-18 | E-GEOD-58657 | biostudies-arrayexpress
Project description:The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base phosphates, other sphingolipids (including sphingosine, ceramide, and sphingomyelin) were substantially elevated in the serum and /or liver of these mice. This latter increase is consistent with a reutilization of the sphingosine backbone for sphingolipid synthesis due to its inability to exit the sphingolipid metabolic pathway. Furthermore, the S1P lyase deficiency resulted in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Even though lipids in serum and lipid storage were elevated in liver, adiposity was reduced in the S1P lyase-deficient mice. Microarray analysis of lipid metabolism genes in liver showed that the S1P lyase deficiency caused widespread changes in their expression pattern. These results demonstrate that S1P lyase is a key regulator of the levels of multiple sphingolipid substrates and reveal functional links between the sphingolipid metabolic pathway and other lipid metabolic pathways that may be mediated by shared lipid substrates and changes in gene expression programs. The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases.
2010-01-28 | GSE18745 | GEO
Project description:Background: Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. Objective: To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. Methods: ASM cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and western blotting. Receptor signalling and function was determined by mRNA knockdown and intracellular calcium mobilisation experiments. Results: S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P2 and S1P3 receptors activated intracellular calcium mobilisation and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals. Conclusion: S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma.
2015-06-18 | GSE58657 | GEO
Project description:Sphingosine 1-phosphate (S1P), a lipid chemoattractant, guides immune cells from the low-S1P environment of tissues into the high-S1P environment of circulatory fluids. Most notably, S1P directs T cell exit from lymph nodes (LN), where T cells are initially activated to fight pathogens, into lymph, from which T cells flow into blood and ultimately reach inflamed tissues. T cells follow these gradients primarily using S1P receptor 1 (S1PR1). The drugs Gilenya and Siponimod, both FDA-approved for the autoimmune disease multiple sclerosis, target S1PR1. They blind self-reactive T cells to S1P gradients, block them from exiting LN, and thus prevent them from infiltrating the central nervous system. While recent work has revealed key aspects of how S1P gradients are established at steady-state, very little is known about S1P distribution in disease, and in turn how changing S1P gradients may affect the immune response. Here, we find that LN S1P increases during an immune response, which prolongs the time T cells spend in the LN before exiting into lymph. Inflammatory monocytes, which had not previously been implicated in shaping S1P gradients, are an important source of this S1P. Inflammatory monocytes must express the early activation marker CD69 to supply S1P to T cells; CD69 represses transcription of S1P receptor 5 (S1pr5), enabling monocytes to infiltrate the LN T zone and efficiently release S1P. Here we compared RNA sequencing of inflammatory monocytes WT or CD69-KO infiltrating the draining lymph node.$
2020-12-23 | GSE139006 | GEO
Project description:Human embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P. Microarrays were used to examine changes in gene expression invoked by treatment of human embryonic stem cells grown upon different matrices Keywords: Karyotypically normal human Esc's
2007-05-25 | GSE7896 | GEO
Project description:Chronic inflammation is associated with disruption of cellular homeostasis, yet the underlying mechanisms remain elusive1. Nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) are intracellular pathogen recognition receptors that activate innate immune responses via sensing bacterial peptidoglycans2-4. We demonstrate that NOD1/2 sense not only microbe-specific molecular patterns but also perturbation of cell homeostasis, and thereby cause inflammation. Host generation of sphingosine-1-phosphate (S1P) via the hydrolysis pathway is essential for NOD1/2 signaling upon such stress. Cytosolic delivery of S1P activates NOD1/2 dependent NF-κB activation and inflammation. Finally, we demonstrate that S1P directly binds to and activates NOD1/2. In sum, we describe a hitherto unknown role of NOD1/2 by revealing that they initiate innate immune responses by surveillance of cellular homeostasis through sensing of cytosolic S1P. Our findings provide a novel link between host cytosolic S1P and NOD1/2 mediated immune activation upon perturbation of cellular homeostasis and thus form the basis for future intervention strategies targeting the S1P-NOD1/2 axis.
2020-01-01 | GSE124828 | GEO
Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis. Comparison of KO vs. WT with five replications per treatment sample
2013-08-09 | E-GEOD-40368 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P. Microarrays were used to examine changes in gene expression invoked by treatment of human embryonic stem cells grown upon different matrices Experiment Overall Design: Human embryonic stem cells (Sheff 4) were grown upon MEFs. One group were treated with S1P. Each group consisted of three replicates which were hybridised to Human U133 plus 2 Affymetrix GeneChips
2009-04-30 | E-GEOD-7896 | biostudies-arrayexpress